Experienced carotid surgeons know that when performing a carotid endarterectomy, it is important to avoid excessive manipulation of the carotid bifurcation during dissection, especially when the patient has had recent symptoms from an “active” plaque. This study by Fisher et al comparing the pathology of carotid plaques obtained from the asymptomatic carotid endarterectomy trial, ACAS, to those taken from the symptomatic trial, NASCET, helps explain the danger. Plaques resected from symptomatic patients are more frequently ulcerated and have attached thrombus compared with asymptomatic plaques and, therefore, are at greater risk to embolize clot and atherosclerotic debris into the cerebral circulation during surgical mobilization. During carotid endarterectomy, the tube-like carotid plaque is cut length-wise and not infrequently torn, preventing a highly accurate gross or microscopic assessment. This might explain why the associations between ulcers, thrombus, and ipsilateral symptoms were not found to be even stronger. In the study reported here, ulceration has a similar frequency in either carotid of a patient with unilateral symptoms, and thrombus was relatively common in plaques not causing symptoms, being present in 21% of plaques in which the symptoms were from the contralateral carotid and 18% of asymptomatic patients. Trends detected in this study (not reaching statistical significance) included the greater prevalence of plaque thrombus when symptoms were closer to the time of surgery (29% for symptoms ≤30 days versus 19% for symptoms >30 days from surgery) and the greater prevalence of thrombus in those symptomatic patients with stroke (35%) than those with transient ischemic attack (18%).

Is there anything in this study we can apply to patients in the clinic? As suggested, it might partly explain the frequent observation that carotid endarterectomy seems safer in asymptomatic than symptomatic patients.1 Does it in any way help us to better-select patients for carotid endarterectomy? The authors suggest that asymptomatic plaques found opposite to symptomatic plaques in the same patients are more commonly ulcerated with attached thrombus and, therefore, perhaps more dangerous. But they remind us also that ulceration and intraluminal thrombus are sometimes difficult to detect with carotid imaging, and this is particularly true with carotid ultrasound and contrast magnetic resonance angiography. So, I am not sure how further ahead we are with the information provided in this report.

Is it in fact possible to determine which asymptomatic carotid plaques have the greatest risk of causing future stroke, therefore justifying consideration of prophylactic repair? Suggested risk factors include male sex,2 ipsilateral brain infarction on brain imaging,3 plaque ulceration detectable on angiography,4–8 the presence of an occluded contralateral carotid artery,9 a stenosis that worsens over time,10 a partly echolucent or heterogenous (“soft”) plaque or evidence of intraplaque hemorrhage on ultrasound,10–14 carotid wall “stiffness” or distensibility during the cardiac cycle,15 and the presence of microemboli detected distal to the plaque on transcranial Doppler.16 Of course, younger patients stand to benefit more from carotid endarterectomy than an elderly person with asymptomatic stenosis. Interestingly, higher degrees of arterial narrowing caused by plaque, an important risk factor for symptomatic stenosis17 and an intuitive and commonly considered risk factor for asymptomatic patients, was not found to correlate with surgical benefit in either ACAS18 or the recently published Asymptomatic Carotid Surgery Trial (ACST).19 Perhaps in the future, chemical composition of carotid plaques as determined by magnetic resonance spectroscopy or molecular markers in either the plaque or serum will be found to correlate with stroke risk,20 but a powerful relationship would be required for a significant correlation to exist, given the overall relatively benign natural history of asymptomatic plaques.

We continue to consider asymptomatic carotid stenosis to be an “uncertain” indication for carotid endarterectomy under any circumstance, requiring individual patient assessment and selection, and surgery should be offered only by expert surgeons with low complication rates.21